Aging is associated with declines in aerobic capacity, exercise tolerance, and functional endurance that lead to physical disability. To date, regular exercise is the only therapy to consistently improve aerobic function, and perhaps delay the onset of disability. However, some data show that the maximal efficacy of exercise for improving aerobic function is blunted by obesity. In addition, our preliminary data show a potential dose-response benefit of concomitant fat loss on exercise-induced improvements in aerobic function. Thus, combining an exercise intervention with caloric restriction resulting in fat loss may be more efficacious for improving aerobic function than exercise alone in obese elderly, a population at high risk for disability. This study is a 3-arm, 5-month randomized, clinical trial in 180 older (65-79 yrs), obese (BMI=30-34.9 kg/m2), sedentary men and women designed to determine whether the amount of fat loss (achieved through controlled underfeeding) affects the magnitude of improvement in aerobic function (maximal aerobic capacity and endurance) in response to a standardized exercise training stimulus that follows current recommendations. Participants will be randomized to an exercise training intervention (moderate-intensity treadmill walking, 4 d/wk) alone (EX Only), exercise with moderate caloric restriction (-250 kcal/d deficit) designed for low fat loss (EX+Low CR; ~3.4 kg fat loss), or exercise with intensive caloric restriction (-750 kcal/d deficit) designed for high fat loss (EX+High CR; ~10.2 kg fat loss). The Specific Aims are to determine the effects of adding moderate and intensive caloric restriction to a standardized aerobic exercise training intervention on: 1) maximal aerobic capacity and walking endurance (6-minute walking distance); 2) cardiovascular disease risk factors (inflammatory markers, blood lipids, blood pressure, glucose tolerance and endothelial function); and 3) inter- muscular, abdominal visceral and pericardial fat volumes. We will also determine whether improvements in aerobic function and CVD risk factors are related to the degree of total and regional fat loss. If our hypotheses are confirmed, this study will provide the first prospective and definitive evidence from a randomized, controlled trial that loss of fat mass augments exercise-induced improvements in aerobic function. These findings will provide persuasive evidence that addition of caloric restriction to an exercise intervention in older, obese adults may be more effective for improving aerobic function than exercise alone, and are likely to change traditional reluctance to recommend some caloric restriction during an exercise program in older adults for the purpose of maximizing their exercise efforts. In addition, by assessing lipid accumulation around visceral organs, and skeletal and cardiac muscle, before and after the interventions, we will also be able to determine the contribution of fat loss in these local depots to the magnitude of exercise-induced improvement in both functional and CVD risk factor outcomes. PUBLIC HEALTH RELEVANCE: This study will determine whether older, obese men and women who lose more fat during an exercise training program will experience greater improvements in fitness and endurance as a result of the exercise training than those who do not lose any fat, or very little fat. This knowledge could lead to a stronger clinical recommendation for inclusion of weight loss to benefit obese, older individuals who exercise. The results will also provide information on whether the location of fat loss is important for improving fitness and cardiovascular disease risk.